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71.
Large-scale exploration of growth inhibition caused by overexpression of genomic fragments in Saccharomyces cerevisiae
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Boyer J Badis G Fairhead C Talla E Hantraye F Fabre E Fischer G Hennequin C Koszul R Lafontaine I Ozier-Kalogeropoulos O Ricchetti M Richard GF Thierry A Dujon B 《Genome biology》2004,5(9):R72-19
We have screened the genome of Saccharomyces cerevisiae for fragments that confer a growth-retardation phenotype when overexpressed in a multicopy plasmid with a tetracycline-regulatable (Tet-off) promoter. We selected 714 such fragments with a mean size of 700 base-pairs out of around 84,000 clones tested. These include 493 in-frame open reading frame fragments corresponding to 454 distinct genes (of which 91 are of unknown function), and 162 out-of-frame, antisense and intergenic genomic fragments, representing the largest collection of toxic inserts published so far in yeast. 相似文献
72.
Amyloid-Beta Immunization in Alzheimer's Disease Transgenic Mouse Models and Wildtype Mice 总被引:1,自引:0,他引:1
Lemere CA Spooner ET Leverone JF Mori C Iglesias M Bloom JK Seabrook TJ 《Neurochemical research》2003,28(7):1017-1027
Alzheimer's disease is the most prevalent form of dementia worldwide. Therapies are desperately needed to prevent and cure the disease. Mouse models of amyloid- deposition [APP and PSAPP transgenic (tg) mice] have been useful in determining the role of amyloid- (A) in both the pathogenesis and cognitive changes in AD. In addition, they have allowed scientists to investigate potential AD therapies in living animals. Active and passive A immunizations have been employed successfully in APP and PSAPP tg mice to lower cerebral A levels and improve cognition. Optimization of immunization protocols and characterization of immune responses in wildtype mice have been reported. Based on the promising results of A immunization studies in mice, a clinical trial was initiated for A vaccination in humans with AD. Although no adverse effects were reported in the Phase I safety trials, about 5% of AD patients in the phase II clinical trial developed meningoencephalitis, ending the trial prematurely in March 2002. Studies in AD mouse models and wildtype mice may help elucidate the mechanism for these unwanted side effects and will be useful for testing newer, safer vaccines for future use in human clinical trials. 相似文献
73.
An Y Shao Y Alory C Matteson J Sakisaka T Chen W Gibbs RA Wilson IA Balch WE 《Structure (London, England : 1993)》2003,11(3):347-357
Rab GTPases, key regulators of membrane targeting and fusion, require the covalent attachment of geranylgeranyl lipids to their C terminus for function. To elucidate the role of lipid in Rab recycling, we have determined the crystal structure of Rab guanine nucleotide dissociation inhibitor (alphaGDI) in complex with a geranylgeranyl (GG) ligand (H(2)N-Cys-(S-GG)-OMe). The lipid is bound beneath the Rab binding platform in a shallow hydrophobic groove. Mutation of the binding pocket in the brain-specific alphaGDI leads to mental retardation. Strikingly, lipid binding acts through a conserved allosteric switching mechanism to promote release of the GDI-Rab[GDP] complex from the membrane. 相似文献
74.
Grover TR Parker TA Zenge JP Markham NE Kinsella JP Abman SH 《American journal of physiology. Lung cellular and molecular physiology》2003,284(3):L508-L517
Although vascular endothelial growth factor (VEGF) plays a vital role in lung vascular growth in the embryo, its role in maintaining endothelial function and modulating vascular structure during late fetal life has not been studied. We hypothesized that impaired lung VEGF signaling causes pulmonary hypertension, endothelial dysfunction, and structural remodeling before birth. To determine whether lung VEGF expression is decreased in an experimental model of persistent pulmonary hypertension of the newborn (PPHN), we measured lung VEGF and VEGF receptor protein content from fetal lambs 7-10 days after ductus arteriosus ligation (132-140 days gestation; term = 147 days). In contrast with the surge in lung VEGF expression during late gestation in controls, chronic intrauterine pulmonary hypertension reduced lung VEGF expression by 78%. To determine whether VEGF inhibition during late gestation causes pulmonary hypertension, we treated fetal lambs with EYE001, an aptamer that specifically inhibits VEGF(165). Compared with vehicle controls, EYE001 treatment elevated pulmonary artery pressure and pulmonary vascular resistance by 22 and 50%, respectively, caused right ventricular hypertrophy, and increased wall thickness of small pulmonary arteries. EYE001 treatment reduced lung endothelial nitric oxide synthase protein content by 50% and preferentially impaired the pulmonary vasodilator response to ACh, an endothelium-dependent agent. We conclude that chronic intrauterine pulmonary hypertension markedly decreases lung VEGF expression and that selective inhibition of VEGF(165) mimics the structural and physiological changes of experimental PPHN. We speculate that hypertension downregulates VEGF expression in the developing lung and that impaired VEGF signaling may contribute to the pathogenesis of PPHN. 相似文献
75.
Differential expression of fatty acid synthase genes,Acl, Fat and Kas,in Capsicum fruit 总被引:1,自引:0,他引:1
Aluru MR Mazourek M Landry LG Curry J Jahn M O'Connell MA 《Journal of experimental botany》2003,54(388):1655-1664
76.
Perry SS Pierce LJ Slayton WB Spangrude GJ 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(4):1877-1886
Thymic cellularity is maintained throughout life by progenitor cells originating in the bone marrow. In this study, we describe adult mouse bone cells that exhibit several features characteristic of prothymocytes. These include 1) rapid thymic engraftment kinetics following i.v. transplantation, 2) dramatic expansion of thymic progeny, and 3) limited production of hemopoietic progeny other than thymocytes. The adult mouse bone marrow population that is depleted of cells expressing any of a panel of lineage-specific Ags, stem cell Ag-1 positive, and not expressing the Thy1.1 Ag (Thy1.1(-)) (Thy1.1(-) progenitors) can repopulate the thymus 9 days more rapidly than can hemopoietic stem cells, a rate of thymic repopulation approaching that observed with transplanted thymocytes. Additionally, Thy1.1(-) progenitors expand prolifically to generate thymocyte progeny comparable in absolute numbers to those observed from parallel hemopoietic stem cell transplants, and provide a source of progenitors that spans multiple waves of thymic seeding. Nevertheless, the Thy1.1(-) population yields relatively few B cells and rare myeloid progeny posttransplant. These observations describe the phenotype of an adult mouse bone marrow population highly enriched for rapidly engrafting, long-term thymocyte progenitors. Furthermore, they note disparity in B and T cell expansion from this lymphoid progenitor population and suggest that it contains the progenitor primarily responsible for seeding the thymus throughout life. 相似文献
77.
Tang RS Schickli JH MacPhail M Fernandes F Bicha L Spaete J Fouchier RA Osterhaus AD Spaete R Haller AA 《Journal of virology》2003,77(20):10819-10828
78.
79.
Kornblatt JA Marchal S Rezaei H Kornblatt MJ Balny C Lange R Debey MP Hui Bon Hoa G Marden MC Grosclaude J 《Biochemical and biophysical research communications》2003,305(3):518-522
The cellular prion protein (PrP(c)) forms complexes with plasminogen. Here, we show that the PrP(c) in this complex is cleaved to yield fragments of PrP(c). The cleavage is accelerated by plasmin but does not appear to be dependent on it. 相似文献
80.